The aims of the proposed research are to study the pathogenesis of eight selected hereditary neurological disorders of mice, and to compare them with and evaluate their usefulness as models of human hereditary neurological and neuromuscular diseases. Our continued major interests are: (a) The systematic clinical, pathological, and basic biochemical investigation of lethargic (lh), NM133, and jolting, (jo), three conditions whose anatomical bases are as yet unknown, except for some preliminary observations in lethargic; (b) the abnormal myelination and development of grey matter in teetering (tn) and ducky (du); (c) the clinical and pathological comparison of neurological syndromes caused by leaner (la) and tottering (tg) and their combination (la/tg) which suggests the possible role of complementation between them; and (d) the possibility of a defect in the protein-fraction of myelin in jpmsd a mutant characterized by a severe deficiency of myelin. Aside from and in addition to genetic factors involved in all mutants, fundamental areas of investigation relate to the structure of normal and pathological myelin, its chemical composition, origin, synthesis, and location and pathways involved in the formation, maintenance, and degradation of myelin, lipid, and protein constituents.